Uterine Manipulation in Surgery for Endometrial Cancer

(MAN-U Trial)

Recruiting at 3 trial locations

Overseen By Anthony Costales, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Anthony Costales, MD

Must not be taking: Progesterone

Disqualifiers: Laparotomic hysterectomy, Pelvic irradiation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

278 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, multi-center, randomized non-inferiority phase III study to evaluate if patients undergoing a minimally invasive surgery for early stage uterine cancer have cancer cells in the fluid that is obtained at the time of their surgery when a uterine manipulator is placed versus patients who do not have a uterine manipulator placed.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on progesterone therapy to treat endometrial cancer, you cannot participate in the trial.

What data supports the effectiveness of this treatment for endometrial cancer surgery?

The research indicates that there is limited evidence on the effectiveness of using a uterine manipulator in endometrial cancer surgery, with concerns about potential tumor spread during surgery. Decisions on its use are often based on surgeon preference and experience rather than strong evidence. ^{1 2 3 4 5}

Is the use of a uterine manipulator generally safe in surgery for endometrial cancer?

The use of a uterine manipulator in minimally invasive surgery for endometrial cancer is generally considered fairly safe, but its application should be tailored to the size and extent of the tumor. Some concerns exist about potential tumor spread during surgery, but recent studies highlight its safety in early-stage cases. ^{1 2 3 4 6}

How does the use of a uterine manipulator in surgery for endometrial cancer differ from other treatments?

The use of a uterine manipulator (UM) in surgery for endometrial cancer is unique because it is a tool used during minimally invasive surgery to improve surgical ergonomics, but its safety and impact on cancer spread are debated. Unlike other treatments, the decision to use a UM is often based on the surgeon's experience and preference, as there is limited evidence on its effect on cancer outcomes. ^{1 2 3 4 6}

Research Team

Anthony Costales, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults over 18 with suspected early stage endometrial cancer, who are fit enough for minimally invasive surgery (MIS) and have no signs of cancer spread outside the uterus. They must be able to follow the study's procedures and not have had pelvic radiation or progesterone therapy for their cancer.

Inclusion Criteria

I am 18 years old or older.

CA 125 testing is optional but, if obtained, must be within lab normal values

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

I am scheduled for a hysterectomy through an abdominal incision.

I am on progesterone therapy for my endometrial cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo minimally invasive surgery for early stage uterine cancer with or without a uterine manipulator

1 day

1 visit (in-person)

Immediate Post-operative

Assessment of positive peritoneal cytology and other surgical outcomes immediately after surgery

Immediately post-surgery

Follow-up

Participants are monitored for surgical morbidity and other outcomes up to 30 days post-surgery

30 days

Treatment Details

Interventions

• Surgery without UM
• Surgery with UM

Trial Overview The study compares outcomes in patients undergoing MIS for early stage uterine cancer using a uterine manipulator (UM) versus those without UM. It aims to see if there's a difference in the presence of cancer cells in surgical fluid between these two methods.

Participant Groups

Group I: Surgery With UM (Arm MAN UA) Experimental Treatment 1 Intervention

Subjects that undergo a MIS approach with a uterine manipulator (experimental arm)

Group II: Surgery Without UM (Arm Control) Active Control 1 Intervention

Subjects that undergo a MIS approach without a uterine manipulator (control arm)

Surgery without UM is already approved in European Union, United States for the following indications:

Approved in European Union as Minimally Invasive Surgery for:

• Early-stage endometrial cancer

Approved in United States as Minimally Invasive Surgery for:

• Early-stage endometrial cancer

Who Is Running the Clinical Trial?

Anthony Costales, MD

Lead Sponsor

Trials

1

Recruited

280+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Findings from Research

In a survey of 165 French onco-gynecologic surgeons, only 42.7% routinely used the uterine manipulator (UM) during minimally invasive hysterectomies for endometrial cancer, with many surgeons (40.9%) avoiding its use due to concerns about the risk of tumor spillage.

Surgeons who did use the UM reported benefits such as reduced operating time (67.0%) and fewer complications (59.8%), but there remains significant variability in practice, highlighting the need for more prospective studies to assess the safety and efficacy of UM in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of uterine manipulator in endometrial cancer: A French survey from Francogyn group. Sallee, C., Lacorre, A., Despoux, F., et al.[2022]

The use of uterine manipulators during minimally invasive surgery for endometrial cancer does not increase the risk of positive peritoneal cytology, lymphovascular space invasion (LVSI), or recurrence, based on a meta-analysis of 11 studies.

The timing of uterine manipulator insertion also showed no significant impact on these outcomes, suggesting that their use is safe in the context of laparoscopic surgery for endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of uterine manipulators in minimally invasive hysterectomy for endometrial cancer: A systematic review and meta-analysis. Meng, Y., Liu, Y., Lin, S., et al.[2020]

In a study of 2661 women with early-stage endometrial cancer, the use of a uterine manipulator during minimally invasive surgery was linked to a higher recurrence rate of 11.69% compared to 7.4% in those who did not use the manipulator, indicating a potential risk associated with its use.

The presence of a uterine manipulator was also associated with lower disease-free survival and a higher risk of death, suggesting that its use may negatively impact oncological outcomes for patients with uterus-confined endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery. Padilla-Iserte, P., Lago, V., Tauste, C., et al.[2021]

In a study of 82 patients undergoing minimally invasive endometrial cancer surgery, a uterine perforation (UP) rate of 11% was observed, indicating a notable risk associated with the use of a uterine manipulator (UM).

While UP did not lead to any positive peritoneal cytology or recurrences, it was associated with a higher rate of lymph-vascular space invasion and resulted in changes to adjuvant therapies for 22% of patients, suggesting potential implications for treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery. Sallée, C., Lacorre, A., Despoux, F., et al.[2023]

In a study comparing 86 robotic surgeries and 67 open surgeries for early-stage endometrial cancer, the use of a uterine manipulator in robotic surgery did not affect oncological outcomes such as recurrence or survival rates.

Robotic surgery resulted in longer operative times but significantly less blood loss, fewer complications, and shorter hospital stays compared to open surgery, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the use of a uterine manipulator in robotic surgery for early-stage endometrial cancer affect oncological outcomes? Ito, H., Moritake, T., Isaka, K.[2022]

The use of uterine manipulators (UM) during laparoscopic total hysterectomy for early-stage endometrial cancer (EC) is generally considered safe, as supported by a review of 11 eligible studies.

While all types of UMs are deemed fairly safe, their application should be customized based on the tumor's size and the extent of myometrial infiltration to minimize risks such as iatrogenic lymphovascular space invasion (LVSI) and retrograde tumor spillage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of uterine manipulator during laparoscopic endometrial cancer treatment. Capozzi, VA., Rosati, A., Uccella, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Use of uterine manipulator in endometrial cancer: A French survey from Francogyn group. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The effects of uterine manipulators in minimally invasive hysterectomy for endometrial cancer: A systematic review and meta-analysis. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Does the use of a uterine manipulator in robotic surgery for early-stage endometrial cancer affect oncological outcomes? [2022]

6. China pubmed.ncbi.nlm.nih.gov

Role of uterine manipulator during laparoscopic endometrial cancer treatment. [2022]